Introduction: Linear accelerator (Linac) based stereotactic radiosurgery (SRS) and stereotactic radiotherapy (SRT) using volumetric modulated arc therapy (VMAT) has been used for treating small intracranial lesions. Recent development in the Linacs such as inbuilt micro multileaf collimator (MLC) and flattening filter free (FFF) beam are intended to provide a better dose conformity and faster delivery when using VMAT technique. This study was aimed to compare the dosimetric outcomes and monitor units (MUs) of the stereotactic treatment plans for different commercially available MLC models and beam profiles. Materials and Methods: Ten patients having 12 planning target volume (PTV)/gross target volume's (GTVs) who received the SRS/SRT treatment in our clinic using Axesse Linac (considered reference arm gold standard) were considered for this study. The test arms comprised of plans using Elekta Agility with FFF, Elekta Agility with the plane beam, Elekta APEX, Varian Millennium 120, Varian Millennium 120HD, and Elekta Synergy in Monaco treatment planning system. Planning constraints and calculation grid spacing were not altered in the test plans. To objectively evaluate the efficacy of MLC-beam model, the resultant dosimetric outcomes were subtracted from the reference arm parameters. Results: V95%, V100%, V105%, D1%, maximum dose, and mean dose of PTV/GTV showed a maximum inter MLC - beam model variation of 1.5% and 2% for PTV and GTV, respectively. Average PTV conformity index and heterogeneity index shows a variation in the range 0.56–0.63 and 1.08–1.11, respectively. Mean dose difference (excluding Axesse) for all organs varied between 1.1 cGy and 74.8 cGy (mean dose = 6.1 cGy standard deviation [SD] = 26.9 cGy) and 1.7 cGy–194.5 cGy (mean dose 16.1 cGy SD = 57.2 cGy) for single and multiple fraction, respectively. Conclusion: The dosimetry of VMAT-based SRS/SRT treatment plan had minimal dependence on MLC and beam model variations. All tested MLC and beam model could fulfil the desired PTV coverage and organs at risk dose constraints. The only notable difference was the halving of the MU for FFF beam as compared to the plane beam. This has the potential to reduce the total patient on couch time by 15% (approximately 2 min).

The basic challenge with any of these techniques is to deliver a conformal dose distribution and reduce dose to the organs at risk (OAR). All aforementioned techniques have their pros and cons. Stereotactic cone based planning is time-consuming and can compromise conformity of target dose coverage or sparing of normal tissue. Therapy delivery using multiple cones is also laborious and time-consuming. The main disadvantage of CD-ARC is its inability to produce fluence modulation; intensity modulated radiotherapy (IMRT) is a better choice for OAR sparing but again suffers from increased treatment delivery time. Volumetric modulated arc therapy (VMAT)based SRS can overcome many of the problems with above techniques.[3] VMAT produces an inversely optimized plan with a definite sparing of the OAR while retaining the advantage of reduced delivery time.[4],[5]

One of the main advantages exploited by VMAT technique for stereotactic planning is the ability to conform the dose distribution to the planning target volume (PTV), providing a steep dose gradient between the PTV and the surrounding normal tissues.

Over the past decade, there have been steady advances in Linacs, including the advent of micro MLCs (mMLCs) and flattening filter free (FFF) beams. Intuitively, these advancements when added up to VMAT should ideally produce a significant improvement in dosimetry. The efficacy of miniature MLC while having been studied in the context of pre-VMAT era needs re-evaluation with an advanced delivery technique like VMAT.[6],[7] This study was aimed to assess whether using miniature MLC and FFF beam improves stereotactic treatment planning.

» Materials and Methods

Ten patients were incorporated in this study. These patients had earlier been planned and treated with frameless SRS or SRT in our clinic.

Patient immobilization and simulation

The patients to be planned for SRS/SRT were placed supine on the simulator couch in head first supine position. A fine mesh, multiple layer thermoplastic casts from Brainlab (Brainlab AG, Feldkirchen, Germany) was used for immobilization. An external computed tomography (CT) localizer (Brainlab head neck localizer) and infrared marker assembly were used for localization and generating the stereoscopic coordinate system. Patient CT simulation was performed on a 64 slice scanner (true-flight select from Philips) system along with immobilization cast and CT localizer and axial images with 1.5 mm thickness were acquired. The images were directly transferred to the iPlan planning system for localization using DICOM enabled protocol.

Contouring

Different magnetic resonance imaging (MRI) sequences (T1-weighted, T2 flair, and constructive interference in steady state) were acquired for radiotherapy planning purpose to facilitate the tumor and normal tissue contouring. Uniform 1 mm margin was given to gross target volume (GTV) to grow PTV. All contours including GTV/PTV were contoured on MRIs and transferred to CT scan after mutual information registration.

The standard arm for the study was Axesse and rest of the MLC-beam models were considered as test arms.

Treatment planning

Contoured images were localized for stereotactic coordinates in the iPlan system (version 4.1.1, Brainlab, Feldkirchen, Germany). The image sets were pushed for treatment planning to CMS MONACO (V5.20.01) (CMS Elekta, Sunnyvale, CA, USA) using DICOM enabled protocol. Stereotactic coordinate (isocenter) between the iPlan and Monaco was kept the same. Treatment plans were generated using VMAT for 10 patients with twelve PTV's. Our treatment strategy involved two or three partial arc for one-sided tumors and a full arc along with two or one partial arc for central tumors (like pituitary). For right-sided tumors a coplanar beam with gantry (G) rotational angle G150°-180°-0°-30° clockwise (CW) was used. For left-sided tumors, a gantry rotational angle of G210°-180°-0°-330° counter CW (CCW) was used.

Noncoplanar partial arcs where a table (T) angle was used were following; for right-sided tumor partial arc were T25 G0–180 CW, T45 G0–180 CW; for left-sided tumors, partial arcs of T315 G0–180 CCW and T335 G0–180 CCW were used. Treatment plan already generated in the Axesse for patient treatment delivery was considered the control arm. Further test plans were generated without altering any optimization parameters and calculation grid spacing. Therefore, the archived dosimetric results in different planning were exclusively influenced by beam and MLC model.

[Figure 1] shows a typically treated case of CP angle left vestibular schwannoma. Tumor embedded between the left cochlea and the brainstem. Three rotational arcs, one full coplanar arc and two noncoplanar half arcs of rotational angle 0–180° along with table angles 315° and 335° were used for planning.

Two different fractionation regimens were used for the patients that were taken in this study; single fraction regime and five fraction regime. Out of ten patients, 6 patients were planned for single fraction treatment, whereas 4 patients were considered in multiple fraction regimens. To account for variability in fraction size of single and multiple fraction treatments, the comparative planning data were normalized to the prescription dose.

The presented data for PTV/GTV was obtained by following procedure. First, the difference of evaluation parameter from the reference arm was evaluated. Further, the difference was normalized to the prescription dose to obtain its relative difference. These differences were averaged over the entire patient population to obtain the mean of difference. For OAR, where the data need to be presented in the form of absolute dose or volume two different tables were used for each OAR to present the data.

Conformity index (CI) and heterogeneity index (HI) described in this paper was defined as where Vprescription is the structure volume covered by the dose of interest and VRI the total volume of the dose of interest.

where D5% is the dose delivered to the hottest 5% of the PTV, and D95% is the minimum dose received by 95% of the tissue.

Total eight different dosimetric parameters required for the clinical evaluation of PTV/GTV dose were assessed in this analysis. The parameters were PTV/GTV volume receiving 95% of prescription dose (RXD) (V95%), PTV and GTV volume receiving 100% RXD (V100%), PTV/GTV volume receiving 105% RXD (V105%), percentage dose received by 1% of the PTV/GTV volume, maximum dose of PTV/GTV, and mean dose of PTV/GTV, CI and HI for PTV/GTV.

Following tolerance, doses were followed during the treatment planning and evaluation. For single fraction delivery, the constraints of brainstem maximum dose <15 Gy and 10 Gy to be received by <0.5cc volume, cochlea maximum dose <9 Gy and optic nerve and optic chiasm maximum dose <10 Gy and 8 Gy to be received by <0.2cc volume were followed.[8]

For five fraction delivery brainstem maximum dose <31 Gy and 23 Gy to be received by <0.5cc volume. Cochlea maximum dose to be <25 Gy.[8] Optic nerve and optic chiasm maximum dose <25 Gy and 23 Gy to be received by <0.2cc volume.[8]

» Results

Planning target volume and gross target volume

[Figure 2a] and [Figure 2b] represent the six parameter V95%, V100%, V105%, D1%, maximum dose, and mean dose for PTV and GTV, respectively. The prescription dose-normalized (relative, %) mean of difference was plotted as a function of the beam and MLC model. Error bar indicates the total standard deviation (SD) of the mean of difference. Axesse was considered as normalized reference arm therefore indicated by a zero value in the on mean of difference and SD. The values presented were derived as test arm – control arm and hence a positive value indicates higher dose by test arm, and a negative value indicates lower dose by test arm. The maximum difference for V95% PTV, V100% PTV, V105%, and PTV mean dose were obtained for Synergy (−0.07%, −0.21%, 0.37%, and −0.39%, respectively). APEX showed the highest difference for D1% PTV (−0.34%) VAR_M120HD showed the highest maximum dose difference of −0.53% for both PTV and GTV. A similar result was obtained for GTV. The maximum difference in the parameters of V95% GTV, V100% GTV, and maximum dose was obtained using SYNERGY (−0.04%, −0.21%, and 0.8%, respectively). APEX demonstrated the highest difference of mean V105% GTV of −0.4% and VAR_M120 gave the highest mean dose difference of 0.8%.

Figure 2a: Average of the difference for six different parameters (V95%, V100%, V105%, D1%, maximum dose, and mean dose for planning target volume) generated in six test arm beam and multileaf collimator model to that of reference arm (Axesses plan) in percentage

Figure 2b: Average of the difference for six different parameters (V95%, V100%, V105%, D1%, maximum dose, and mean dose for gross target volume) generated in six test arm beam and multileaf collimator model to that of reference arm (Axesses plan) in percentage

[Figure 3], upper panel present the HI and lower panel indicate the CI. HI PTV and HI GTV ranged between 1.04–1.25 and 1.03–1.21, respectively. The highest HI's of for PTV and GTV were 1.25 and 1.21. These were obtained for SYNERGY in PTV 3 and GTV 4, respectively. However, AG_FFF-GTV4 combination also shared the highest HI of 1.21. PTV HI, averaged over all PTV, for different MLC-beam model combination was 1.08, 1.09, 1.06, 1.08, 1.09, 1.08, and 1.11 for AG_FF, AG_PL, APEX, Axesse, VAR_M120, VAR_M120HD, and SYNERGY, respectively. Mean GTV HI was scored for the same series were 1.07, 1.07, 1.06, 1.07, 1.06, and 1.08, respectively. CI PTV ranged between 0.42 and 0.8. When averaged over all PTV mean CI showed a value of 0.6, 0.6, 0.63, 0.60, 0.61, 0.62, and 0.56 for AG_FFF, AG_PL, APEX, Axesse, VAR_M120, VAR_M120HD, and SYNERGY, respectively. For the same sequence of beam and MLC model, GTV showed a CI of 0.46, 0.45, 0.45, 0.47, 0.45, 0.46, and 0.44, respectively. CI of GTV ranged between 0.31 and 0.7.

Figure 3: Radiation therapy oncology group conformity index and heterogeneity index obtained plotted as a function of the beam and multileaf collimator model

Out of these ten tested cases, only in three occasions it was difficult to achieve OAR dose. In two cases, brainstem was at risk (single fraction delivery) and one case chiasm was at risk (five fraction delivery). It was possible to fulfill the dose-volume criteria in all three cases attributed to beam and MLC model. [Table 2] shows the absolute volume in cc for which brainstem and chiasm receiving more than equal to 10 Gy and 23 Gy, respectively.

Table 2: Brainstem and chiasm dose in absolute volume as a function of beam-MLC model for three challenging cases

OAR considered were brainstem, optic chiasm, right and left optic nerve, right and left cochlea, and right and left eye. For all first six structures (serial organs), we considered the maximum dose, whereas mean doses were reported for both eyes considered to be parallel structures. OAR doses for patients were divided into two groups, single fraction delivery and five fractions delivery as per the difference in their tolerance limits.[8]

[Table 3] represents the difference of the maximum and/or mean doses from the reference dose (Axesse) average over all the patients. For a single fraction delivery of all OAR's VAR_M120 showed the highest maximum dose difference of 29.6 cGy and SYNERGY indicated the highest SD of 70.4 cGy. For a five fraction delivery, SYNERGY showed the highest maximum dose difference 89.3 cGy and APEX showed the highest SD of 161.7 cGy for all tested OARs.

Table 3: Mean difference of maximum dose (serial organs brainstem, optic chiasm, right and left optic nerve, and right and left cochlea) and average difference of mean dose (parallel organs right and left eye) as a function of different beam and MLC model

For patients of SRS (single fraction of 12 Gy), the OAR doses attributed to the different beam and MLC model did not exceed 0.6% from the reference plans (Axesse). Mean SD for all MLC-beam model combination and all OAR ranged between 5.4 cGy and 70.4 cGy.

For a patient with SRS (five fractions), the highest maximum dose difference was obtained for left optic nerve for APEX (−194.5 cGy, i.e. 6.2% of reference dose). The average maximum dose for two organs (left optic nerve and left cochlea) exceeded 100 cGy when treatment plan was generated in APEX. The difference between standard and test arms for any MLC-beam model combination for any organ did not exceed 100 cGy (4%) for a prescription dose of 25 Gy. Patient average mean dose difference and SD for all the organs for all the combination of MLC and beam model was seen in the ranged between −194.5–77.5 and 1.8–258.6 cGy, respectively.

Monitor unit

[Table 4] indicate the required monitor units (MUs) for the delivery of each patient, normalized to the clinically delivered plan of Axesse. In a typical VMAT stereotactic, delivery of 12 Gy requires 3300 MU. In patient 1, the delivery of 12 Gy required 3213.4 MU in Axesse. All plane beams and MLC model such as AG_PL, APEX, Axesse, VAR_M120, and VAR_M120HD showed nearly same MU. Mean and SD of required MU for all plane beams without Axesse was 1.03 and 0.2, respectively. FFF beam (AG_FFF) shows a significantly lower MU for the delivery of the same dose with normalized mean MU of 0.51.

Modern developments in the Linacs include inbuilt miniature MLC and FFF beams. This study was aimed to see if such advances benefit the delivery of SRS and SRT during VMAT delivery. Further, we also aimed to answer if using an FFF beam result in any improvement in the dosimetry of the VMAT-based stereotaxy.

Our study has shown that complete range of beam (plane beam and FFF) generates nearly same PTV-related dose volume parameters in the context of stereotaxy. Moreover, it has also shown that even MLC size width varying from 2.5 mm to 1 cm does not make any difference to the dose volume parameters in the plan. It is important to mention that in the context of VMAT, all beam and MLC model combination respect the desire tumor coverage and all applicable OAR tolerance doses.

It was interesting to investigate the variation of CI, as we realize as a general understanding of classical three-dimensional conformal radiotherapy (3DCRT) concept indicate that the conformity is directly dependent on the MLC width, and finer MLC will give a significant improvement on conformity.

In this study, tested minimum MLC widths were 2.5 mm. 2.5 mm width inbuilt mMLC was available from Varian (VAR_M120HD) however, Elekta can offer it as an attachment to basic Linac. The main disadvantage for the mMLC attachment is it reduced the SSD, and its delivery is very much susceptible to a mechanical and electrical fault. To do a Linac-based SRS/SRT and SBRT for cranial and extracranial lesions mMLC was introduced.[9],[10] Bortfeld et al., described the optimal leaf width is applicable to both 3DCRT and IMRT on the basis of the theoretical formulation without demonstrated the clinical significance using “undulation'' of the dose profile at oblique field edges and concluded optimal MLC width of 1.6–2 mm.[11]

Several authors have reported the impact of collimator leaf width and treatment technique on SRS and radiotherapy plans for intra- and extra-cranial lesions using 3DCRT, dynamic conformal arc, and IMRT planning techniques.[12],[13],[14],[15],[16],[17] We could not identify any reports correlating the efficacy of MLC width using VMAT planning for SRS/SRT. Marrazzo et al., compared 3DCRT-based SRT using the mMLC plan with the beam modulator (Axesse in this study) plans. They demonstrated smaller width MLC leads to a better performance in PTV dose homogeneity and OAR sparing using 3DCRT plans. It was also reported that both MLC respected the OAR constraints.[12] Kubo et al. compared 3DCRT plans from the circular collimator plans with mMLC-based 3DCRT plans. They concluded that a using an MLC width of 1.7–3.0 mm mMLC-based plans for nonspherical targets were easier to generate and deliver when compared with the cone-based system.[13] Wu et al. reported the dosimetric impact two different collimator MLC width 2.5 mm and 5 mm for spine tumors, brain tumors, and liver tumors using 3DCRT and IMRT techniques. They concluded the smaller leaf width MLC when combination with the IMRT technique can yield dosimetric benefits in radiosurgery and hypofractionated radiotherapy. Treatment of small lesions in cases involving complex target/OAR geometry will especially benefit from the use of a fine leaf width MLC and the use of IMRT.[14] Monk et al. described the dosimetric impact of 3 mm and 5 mm width MLC leaf for 14 patients using the 3DCRT technique. They found mMLC (3 mm) improves the SRS/SRT treatment plans very marginally. They also argued for the choice of MLC for SRT can also be 5 mm leaf.[15] Dvorak et al. described the impact of intensity modulated technique and MLC leaf width with respect to standard conformal treatment techniques for SBRT in lung and liver lesions. They reported that IMRT gives no improvement on target coverage over the dynamic arc plans.[16] Tanyi et al. compared the performance of 2.5 mm width MLC with 5 mm width MLC for 68 cranial lesions using 3DCRT, IMRT, and CD-ARC. They concluded smaller width MLC shows a better dose conformity and better OAR sparing.[17] Literature review concluded although several investigators have reported an improvement of the dosimetric quality of the SRS/SRT treatment plans for smaller MLC width; however, this finding is not sacrosanct. At least two investigators reported no or insignificant change of the treatment plan quality generated by finer and wider width MLC.[15],[16] Our study reported no improvement of treatment plan quality for a finer width MLC if VMAT is used as the planning modality. This study first of its kind to describe the Influence of MLC width and beam model on VMAT-based stereotactic treatment planning.

In our study, all the tested parameters except the maximum dose attributed to PTV did not vary by more than 1%. Variation went up to 1.5% if the maximum dose was taken into account. For GTV, variation for all tested parameters was found to be within 2%. Variation of CI for both PTV and GTV was insignificant in our study.

The SD of HI for GTV also showed a similar trend with no or very minimal variation credited to MLC and beam model. It can, therefore, be stated that PTV/GTV related dosimetric parameters were not altered by different beam characteristic and MLC width.

It needs to be pointed out that out of ten patients and 12 PTV/GTVs, only three cases had OARs were positioned in a challenging manner with respect to PTV. For such PTVs also there is no significant difference attributed to beam and MLC model. No advantage of smaller width MLC is observed on OAR sparing. All the beam and MLC model satisfy the desired dose constraints.[8] In our center, which treats approximately 40 SRS patients per year, we have observed that nearly 30–40% cases will have a challenging OAR. Among these cases, the majority will have a lone OAR and the minority will have two or more OARs in close vicinity. [Figure 1] demonstrates one such case where PTV is sandwiched between two OARs brainstems and left cochlea.

MU comparison between FFF beams with flat beams indicates a significant difference between them. FFF produces desired dose distribution using only half of the MU to that of the flat beams. However, it can be questioned whether this is a significant advantage or not. VMAT-based stereotactic delivery takes about 4 min in our clinic using Axesse MLC and flat beam model. On an average, the imaging and patient setup time is about 6–7 min. The overall patient on couch time, therefore, is nearly 10–12 min. Halving of the MU produced by FFF will reduce the treatment delivery time to 2 min. However, this shall not reduce the patient on couch time very significantly since the setup time and imaging time essentially remain unaffected. The other possible benefit with FFF is the aspect of fewer MUs leading to a lesser scatter dose, and this aspect needs a more systematic study.

» Conclusion

This study has shown that in a VMAT-based stereotactic delivery, MLC thickness has no or very minimal significance. A 1 cm MLC can produce a dosimetric result equivalent to that of a 2.5 mm MLC. Further, there is no dosimetric advantage of FFF beam over the flat beams except a 15% reduction in overall treatment delivery time.

Dose fall-off patterns with volumetric modulated arc therapy and three-dimensional conformal radiotherapy including the “organ at risk” effect. Experience of linear accelerator-based frameless radiosurgery from a single institution